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JCEM Case Reports Nov 2023Currently, no published cases report concomitant X-linked hypophosphatemia (XLH) and adult hypophosphatasia (HPP). Both diseases share clinical phenotypes that are...
Currently, no published cases report concomitant X-linked hypophosphatemia (XLH) and adult hypophosphatasia (HPP). Both diseases share clinical phenotypes that are almost indistinguishable. The correct diagnosis may be missed without a standardized laboratory and genetic testing approach. Pathogenic variants in the phosphate regulating endopeptidases homolog X-linked gene () and the tissue-nonspecific alkaline phosphatase gene () are genes that cause XLH and HPP, respectively. We describe a concomitant yet undescribed genetic pathogenic variant in a family. A 61-year-old woman was referred by orthopedic surgery for the presence of bilateral leg bowing and short stature during the assessment of knee surgery. The patient had a biochemical workup relevant for low serum phosphorus and 1,25-dihydroxy vitamin D and normal alkaline phosphatase (ALP). Genetic analysis revealed pathogenic variants in and . Her 42-year-old daughter shared identical symptoms and genetic variants with her mother. Both patients started conventional treatment for XLH with phosphorus and vitamin D, and the daughter later switched to burosumab-twza. Adult XLH and HPP may have similarities in clinical presentation but differ in some essential laboratory findings. Normal ALP levels helped direct our diagnosis toward XLH. However, the diagnosis was challenging due to the presence of concurrent variants in the genes involved. These variants illustrate the significant heterogeneity of the clinical expression.
PubMed: 38077305
DOI: 10.1210/jcemcr/luad151 -
Clinical Case Reports Dec 2023Tumor-induced osteomalacia is a paraneoplastic syndrome characterized by renal phosphate wasting and deranged bone turnover. Clinicians should consider tumor-induced...
KEY CLINICAL MESSAGE
Tumor-induced osteomalacia is a paraneoplastic syndrome characterized by renal phosphate wasting and deranged bone turnover. Clinicians should consider tumor-induced osteomalacia in unexplained hypophosphatemia and investigate for underlying tumors.
ABSTRACT
Tumor-induced osteomalacia (TIO) is a rare paraneoplastic syndrome characterized by renal phosphate wasting, which leads to deranged bone turnover. TIO is usually associated with benign mesenchymal tumors, although it has also been reported in malignant tumors. We present the case of a 56-year-old individual who experienced a protracted 6-year clinical course characterized by hypophosphatemia, weakness, and kyphosis, alongside the presence of a foot tumor. Subsequently, this lesion displayed malignant behavior and was ultimately diagnosed as a high-grade sarcoma. To date, this case is among the 10 reported cases in the literature of a mesenchymal tumor associated with TIO undergoing malignant transformation. This report underscores the importance of a comprehensive evaluation of patients with unexplained hypophosphatemia and highlights the need for diligent follow-up to detect possible malignant transformation of the underlying tumor. Clinicians should consider TIO in the differential diagnosis of hypophosphatemia and promptly investigate for the presence of an underlying tumor, as early detection may improve the patient's prognosis.
PubMed: 38076012
DOI: 10.1002/ccr3.8283 -
World Journal of Clinical Cases Nov 2023Osteomalacia (OM) is frequently confused with various musculoskeletal or other rheumatic diseases, especially in patients with adult-onset widespread musculoskeletal...
BACKGROUND
Osteomalacia (OM) is frequently confused with various musculoskeletal or other rheumatic diseases, especially in patients with adult-onset widespread musculoskeletal pain because of its low prevalence and non-specific manifestations.
AIM
To facilitate the early diagnosis and etiology-specific treatment of adult-onset hypophosphatemic OM.
METHODS
A retrospective review of medical records was performed to screen adult patients who visited a physiatry locomotive medicine clinic (spine and musculoskeletal pain clinic) primarily presenting with widespread musculoskeletal pain at a single tertiary hospital between January 2011 and December 2019. We enrolled patients with hypophosphatemia, high serum bone-specific alkaline phosphatase levels, and at least one imaging finding suggestive of OM.
RESULTS
Eight patients with adult-onset hypophosphatemic OM were included. The back was the most common site of pain. Proximal dominant symmetric muscle weakness was observed in more than half of the patients. Bone scintigraphy was the most useful imaging modality for diagnosing OM because radiotracer uptake in OM showed characteristic patterns. Six patients were diagnosed with adefovir (ADV)-induced Fanconi syndrome, and the other two patients were diagnosed with tumor-induced OM and light-chain nephropathy, respectively. After phosphorus and vitamin D supplementation and treatment for the underlying etiologies, improvements in pain, muscle strength, and gait were observed in all patients.
CONCLUSION
Mechanical pain characteristics, hypophosphatemia, and distinctive bone scintigraphy patterns are the initial diagnostic indicators of adult-onset hypophosphatemic OM. ADV-induced Fanconi syndrome is the most common etiology of hypophosphatemic OM in hepatitis B virus-endemic countries.
PubMed: 38073682
DOI: 10.12998/wjcc.v11.i32.7785 -
FEBS Open Bio Feb 2024Congenital fibroblast growth factor 23 (FGF23)-related hypophosphatemic rickets/osteomalacia is a rare bone metabolism disorder characterized by hypophosphatemia and...
Congenital fibroblast growth factor 23 (FGF23)-related hypophosphatemic rickets/osteomalacia is a rare bone metabolism disorder characterized by hypophosphatemia and caused by genetic abnormalities that result in excessive secretion of FGF23. Hyp mice are a model of X-linked hypophosphatemia (XLH) caused by deletion of the PHEX gene and excessive production of FGF23. The purpose of this study was to investigate the potential of TM5614 as a therapeutic agent for the treatment of congenital FGF23-related hypophosphatemic rickets and osteomalacia in humans by administering TM5614 to Hyp mice and examining its curative effect on hypophosphatemia. After a single oral administration of TM5614 10 mg·kg to female Hyp mice starting at 17 weeks of age, the serum phosphate concentration increased with a peak at 6 h after administration. ELISA confirmed that TM5614 administration decreased the intact FGF23 concentration in the blood. Expression of 25-hydroxyvitamin D-1α-hydroxylase protein encoded by Cyp27b1 mRNA in the kidney was suppressed in Hyp mice, and treatment with 10 mg·kg of TM5614 normalized the expression of 25-hydroxyvitamin D-1α-hydroxylase protein and Cyp27b1 mRNA in the kidneys of these mice. Our data indicate that oral administration of TM5614 ameliorates hypophosphatemia in Hyp mice, suggesting that TM5614 may be an effective treatment for congenital FGF23-related hypophosphatemic rickets and osteomalacia.
Topics: Mice; Female; Humans; Animals; Familial Hypophosphatemic Rickets; Plasminogen Activator Inhibitor 1; Osteomalacia; 25-Hydroxyvitamin D3 1-alpha-Hydroxylase; Hypophosphatemia; RNA, Messenger
PubMed: 38050660
DOI: 10.1002/2211-5463.13745 -
International Journal of Paleopathology Mar 2024Cribra orbitalia is believed to be a skeletal indicator of chronic anaemia, scurvy, rickets or related metabolic diseases. It has been suggested that it may be used as a...
OBJECTIVE
Cribra orbitalia is believed to be a skeletal indicator of chronic anaemia, scurvy, rickets or related metabolic diseases. It has been suggested that it may be used as a proxy indicator for intestinal parasite infection, as parasites often cause anaemia today. Our aim is to investigate this association in the medieval population of Cambridge, UK.
MATERIALS
Individuals excavated from the cemeteries of the Augustinian friary and All Saints by the Castle parish church, and aged from 7 to adulthood.
METHODS
We undertook parasite analysis of the pelvic sediment and control samples of 46 burials with intact orbital roofs.
RESULTS
Human roundworm (Ascaris lumbricoides) and/or whipworm (Trichuris trichiura) were identified in the pelvic sediment of 22 individuals, and cribra orbitalia noted in 11 individuals. Barnards test showed no association between parasite infection and cribra orbitalia (p = .882).
CONCLUSION
We found no association between infection and cribra orbitalia infection in this medieval adult population, calling into question this hypothesis, at least for adults.
SIGNIFICANCE
High or low cribra orbitalia prevalence in adults should not be used to infer rates of intestinal parasite infection.
LIMITATIONS
The individuals in the study were over the age of 7, with no younger children. It is possible that only parasites which cause marked anaemia (such as hookworm, schistosomiasis or malaria) may cause cribra orbitalia, while less marked anaemia from roundworm and whipworm may not do so.
SUGGESTIONS FOR FURTHER RESEARCH
Repeating this study in younger children, when most cribra orbitalia appears to form.
Topics: Adult; Child; Humans; Orbit; Intestinal Diseases, Parasitic; Rickets; Anemia; United Kingdom
PubMed: 38039702
DOI: 10.1016/j.ijpp.2023.11.001 -
JPMA. the Journal of the Pakistan... Nov 2023Allotriophagy is defined as food cravings that are different from the expected or the norm. It gives clinical pointers to an underlying diagnosis. We propose a new term,...
Allotriophagy is defined as food cravings that are different from the expected or the norm. It gives clinical pointers to an underlying diagnosis. We propose a new term, allotriodipsia which suggests a preference for beverages that are different from the norm. Taken together, these two entities may point towards certain endocrinological abnormalities and iatrogenic sequelae. In this communication we highlight the clinical relevance of allotriophagy and allotriodipsia.
Topics: Humans; Pica; Endocrine System Diseases
PubMed: 38013549
DOI: 10.47391/JPMA.23-93 -
Osteoporosis International : a Journal... Jan 2024Hypophosphatasia (HPP) is a rare inborn error of metabolism that presents variably in both age of onset and severity. HPP is caused by pathogenic variants in the ALPL... (Review)
Review
Hypophosphatasia (HPP) is a rare inborn error of metabolism that presents variably in both age of onset and severity. HPP is caused by pathogenic variants in the ALPL gene, resulting in low activity of tissue nonspecific alkaline phosphatase (TNSALP). Patients with HPP tend have a similar pattern of elevation of natural substrates that can be used to aid in diagnosis. No formal diagnostic guidelines currently exist for the diagnosis of this condition in children, adolescents, or adults. The International HPP Working Group is a comprised of a multidisciplinary team of experts from Europe and North America who have expertise in the diagnosis and management of patients with HPP. This group reviewed 93 papers through a Medline, Medline In-Process, and Embase search for the terms "HPP" and "hypophosphatasia" between 2005 and 2020 and that explicitly address either the diagnosis of HPP in children, clinical manifestations of HPP in children, or both. Two reviewers independently evaluated each full-text publication for eligibility and studies were included if they were narrative reviews or case series/reports that concerned diagnosis of pediatric HPP or included clinical aspects of patients diagnosed with HPP. This review focused on 15 initial clinical manifestations that were selected by a group of clinical experts.The highest agreement in included literature was for pathogenic or likely pathogenic ALPL variant, elevation of natural substrates, and early loss of primary teeth. The highest prevalence was similar, including these same three parameters and including decreased bone mineral density. Additional parameters had less agreement and were less prevalent. These were organized into three major and six minor criteria, with diagnosis of HPP being made when two major or one major and two minor criteria are present.
Topics: Adult; Child; Humans; Adolescent; Hypophosphatasia; Alkaline Phosphatase; Europe; Prevalence; Mutation
PubMed: 37982855
DOI: 10.1007/s00198-023-06843-2 -
Calcified Tissue International Dec 2023Tumor-induced osteomalacia (TIO) is an ultra-rare disease caused mostly by benign tumors that secrete fibroblast growth factor-23. Because of nonspecific symptoms, the...
Tumor-induced osteomalacia (TIO) is an ultra-rare disease caused mostly by benign tumors that secrete fibroblast growth factor-23. Because of nonspecific symptoms, the diagnostic delay is long, and therapy can be challenging. Moreover, epidemiological data on TIO are scarce owing to its rarity. Therefore, this study aimed to quantify TIO's incidence rates and prevalence in Germany. Retrospective longitudinal and cross-sectional analyses were conducted using anonymized German claims data from the statutory health insurance (SHI) database. This database, which comprises the data of approximately 5 million insurants, is a representative sample of the German population and supports national projections. As there is no unique International Statistical Classification of Diseases and Related Health Problems (ICD) code for TIO, operational categories based on different surrogates were defined to determine the prevalence and incidence rates of TIO among probable patients. This study showed that TIO has a prevalence of (documented code, advanced imaging, medication, or tumor removal) 0.187 per 100,000 persons and an incidence rate of ≤ 0.094 per 100,000 person years. This analysis provides the first epidemiological insight into German patients with TIO. Despite the general limitations associated with the analysis of SHI claims data of ultra-rare diseases, we believe that this analysis provides a sound basis for further analysis, particularly with regard to the care situation of patients with TIO.
Topics: Humans; Retrospective Studies; Cross-Sectional Studies; Delayed Diagnosis; Osteomalacia; Germany
PubMed: 37980279
DOI: 10.1007/s00223-023-01148-2 -
Problemy Endokrinologii Nov 2023Tumor-induced osteomalacia is an acquired rare disease manifested by hypophosphatemic osteomalacia due to excessive secretion of fibroblast growth factor 23 (FGF23). FGF...
INTRODUCTION
Tumor-induced osteomalacia is an acquired rare disease manifested by hypophosphatemic osteomalacia due to excessive secretion of fibroblast growth factor 23 (FGF23). FGF 23 is a non-classical hormone secreted by bone tissue (osteocytes) and regulates phosphorus metabolism.The aim of this work is to present clinical experience in the diagnosis, treatment and rehabilitation of patients with tumor-induced osteomalacia.
MATERIALS AND METHODS
40 patients with clinically-confirmed tumor-induced osteomalacia were included in the study, 34 of whom had the tumor localized, 27 underwent surgical treatment and 21 achieved stable remission.
RESULTS
The median age was 48 [41; 63] years, 43% were men, the time left from the the onset of the disease was 8 [4; 10] years. Biochemical findings were hypophosphatemia 0.47 [0.4; 0.53] mmol/l, a decrease in the tubular reabsorption phosphate 62 [52; 67]%, and an increase in alkaline phosphatase of 183 [112; 294] units/l. At the time of diagnosis, 100% had multiple pathological fractures, only 10% could move independently, and 77.5% classified the pain as unbearable (8-10 points according to the 10-point pain syndrome scale ). Among the methods used to detect tumors, the most sensitive were scintigraphy with tectrotide with SPECT/CT 71.4% (20/28) and MRI 90% (18/20). In 35% of cases, the tumor was localized in soft tissues and in 65% in bone tissue; The tumor was most often detected in the lower extremities, followed by the head in frequency of localization. 18 patients currently have no remission and they receive conservative treatment (phosphorus and alfacalcidol n=15 and burosumab n=3). In case of achieving remission (n=21), regression of clinical symptoms and restoration of bone and muscle mass was observed. Extensive excision of the tumor without prior biopsy resulted in the best percentage of remission - 87%.
CONCLUSION
Tumor-induced osteomalacia is characterized by severe damage to bone and muscle tissue with the development of multiple fractures, muscle weakness and severe pain syndrome. In laboratory diagnostics, attention should be paid to hypophosphatemia, a decrease in the tubular reabsorption phosphate index and increased alkaline phosphatase. The use of functional diagnostic methods with a labeled somatostatin analogue to the subtype 2 receptor and MRI with contrast enhancement are the most accurate methods of topical diagnostics. In case of localization of the tumor, a wide excision without a preliminary biopsy is recommended.
Topics: Male; Humans; Middle Aged; Female; Neoplasms, Connective Tissue; Alkaline Phosphatase; Hypophosphatemia; Phosphates; Phosphorus; Pain
PubMed: 37968949
DOI: 10.14341/probl13221 -
Health Informatics Journal 2023Vitamin D is among the vitamins necessary for both adults' and children's health. It plays a significant role in calcium absorption, the immune system, cell...
Vitamin D is among the vitamins necessary for both adults' and children's health. It plays a significant role in calcium absorption, the immune system, cell proliferation and differentiation, bone protection, skeletal health, rickets, muscle health, heart health, disease pathogenesis and severity, glucose metabolism, glucose intolerance, varying insulin secretion, and diabetes. Because the 25-hydroxyvitamin D (25OHD) test, which is used to measure vitamin D is expensive and may not be covered in healthcare benefits in many countries, this study aims to predict vitamin D deficiency in diabetic patients. The prediction method is based on data mining techniques combined with feature selection by using historical electronic health records. The results were compared with a filter-based feature selection algorithm, namely relief-F. Non-valuable features were eliminated effectively with the relief-F feature selection method without any performance loss in classification. The performances of the methods were evaluated using classification accuracy (ACC), sensitivity, specificity, F1-score, precision, kappa results, and receiver operating characteristic (ROC) curves. The analyses have been conducted on a vitamin D dataset of diabetic patients and the results show that the highest classification accuracy of 97.044% was obtained for the support vector machines (SVM) model using radial kernel that contains 18 features.
Topics: Adult; Child; Humans; Vitamin D Deficiency; Vitamin D; Algorithms; Diabetes Mellitus; Data Mining
PubMed: 37963409
DOI: 10.1177/14604582231214864